NCT06233110 Ruxolitinib Plus Fostamatinib for Steroid Refractory cGvHD
| NCT ID | NCT06233110 |
| Status | Recruiting |
| Phase | Phase 1 |
| Sponsor | Stefanie Sarantopoulos, MD, PhD. |
| Condition | Chronic Graft Versus Host Disease |
| Study Type | INTERVENTIONAL |
| Enrollment | 30 participants |
| Start Date | 2025-10-29 |
| Primary Completion | 2029-01-01 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
Phase 1 is the earliest stage of human testing — safety and dosage are the primary focus. Visits are frequent and medical supervision is intensive. You will be among the first people to receive this treatment.
This trial targets 30 participants in total. It began in 2025-10-29 with a primary completion date of 2029-01-01.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief Summary
This is an open-label phase I study of fostamatinib in combination with ruxolitinib for the treatment of chronic GvHD with a suboptimal response to corticosteroids. The primary objective is to identify a minimum safe and biologically effective dose of fostamatinib when combined with standard of care ruxolitinib for the treatment of steroid refractory and steroid dependent cGVHD. The secondary objective is to estimate the efficacy of the combination of ruxolitinib and fostamatinib for the treatment of steroid refractory and steroid dependent cGVHD. The target enrollment is 24-30 subjects. The study will begin with an initial dose escalation cohort employing a modified 3+3 design to investigate up to three doses of fostamatinib. Using safety, efficacy, pharmacodynamic (PD), and pharmacokinetic data (PK), an interim assessment will be performed to determine two candidate doses of the biologically optimal dose to investigate further. A safety expansion cohort will be opened to backfill these two candidate doses up to a total 12 patients per dose, including those in the dose escalation cohort who received the candidate doses. Patients will then be randomized to one of these two candidate doses in the expansion. If there is an imbalance in the two expansion cohorts, the remaining patient slots after 1:1 randomization will be sequentially backfilled to a total of 12 patients per cohort. A final analysis of safety, efficacy, and PK/PD data in patients who received the two candidate doses will be conducted to determine a minimum safety and biologically effective dose, which will be the recommended phase II dose (RP2D). The primary hypothesis is that Fostamatinib combined with ruxolitinib is a safe therapy for and has synergistic activity in cGvHD. The recommended phase II dose will be determined by the study investigators in collaboration with the sponsors. The decision to select the recommended phase II dose will occur only after all patients in the part 1 have completed at least 28 days of therapy. The decision will be based on the valuation of all relevant, available data, and not solely on dose-limiting toxicities.
Eligibility Criteria
Inclusion Criteria 1. Patient is able and willing to provide written informed consent prior to any study related screening procedures are performed. 2. Age ≥ 18 years old at the time of informed consent 3. Have undergone allogeneic hematopoietic cell transplantation (HCT) from any donor source (matched unrelated donor, sibling, haploidentical) using bone marrow, peripheral blood, or cord blood stem cells. 4. Adequate bone marrow function defined as: 4.1 Absolute neutrophil count (ANC) ≥ 750 /mm3 4.2 Platelet count ≥ 40,000 /mm3 4.3 Hemoglobin ≥ 8.0 g/dL without transfusion support Note: Use of growth factor supplementation (myeloid, erythroid or megakaryocytic) is permitted to meet eligibility criteria. 5. Patients with clinically diagnosed cGvHD staging of mild to severe according to NIH Consensus Criteria4 prior to Cycle 1 Day 1 and with confirmed steroid refractoriness or steroid dependence irrespective of the concomitant use of a calcineurin inhibitor, as follows: 5.1 Disease progression after administration of a minimum dose of 1.0 mg/kg/day or equivalent for at least 1 week at any time following diagnosis of cGvHD OR 5.2 Disease persistence despite continued treatment with prednisone \> 0.5mg/kg/d or equivalent for at least 4 weeks OR 5.3 Increase to prednisone \> 0.25 mg/kg/d after 1 unsuccessful attempt to taper the dose. 5.4 Recurrence of chronic GVHD after attaining a complete response 5.5 Progression of chronic GVHD after attaining a partial response 6. Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Exclusion Criteria 1. Prior or ongoing treatment with ruxolitinib for treatment of cGvHD for longer than 3 weeks prior to anticipated C1D1. 2. Prior treatment with fostamatinib or another SYK inhibitor for the treatment of acute or chronic GVHD. Prior use of fostamatinib for conditions other than GVHD is permitted. 3. Ongoing systemic therapy for cGvHD other than corticosteroids, calcineurin inhibitor, or mycophenolate mofetil, aside from fewer than 3 weeks of ruxolitinib. Prior ruxolitinib use for the indication of acute GVHD is permitted. 4. Patients with relapsed primary malignancy, or who have been treated for relapse after the allogeneic HCT was performed 5. SR-cGvHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Patients who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible. 6. History of progressive multifocal leuko-encephalopathy (PML) 7. Active uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection progression are present. 8. Clinical evidence of active and clinically significant viral disease including HIV, CMV, HHV-6, HBV, HCV, or BK virus. 9. Patients on mechanical ventilation or have a resting O2 saturation \< 90% by pulse oximetry 10. Clinically significant and uncontrolled cardiovascular disease, including unstable angina, acute myocardial infarction, or stroke within 3 months, or NYHA Class III or IV congestive heart failure. 11. Uncontrolled hypertension with systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg. 12. Creatinine clearance by Cockcroft-Gault of \< 15 mL/min and not on dialysis 13. Total bilirubin \> 3 times ULN, ALT \> 5 times ULN, or AST \> 5 times ULN 14. QTc ≥ 470 ms as calculated by the Fridericia Formula 15. Active pregnancy or breast feeding, or currently seeking active pregnancy 16. Any patient who, in the opinion of the investigator, may not be able to comply with study procedures
Contact & Investigator
Chenyu Lin, MD
PRINCIPAL INVESTIGATOR
Duke Health
Frequently Asked Questions
Who can join the NCT06233110 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, up to 80 Years, studying Chronic Graft Versus Host Disease. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT06233110 trial and what does that mean for participants?
Phase 1 trials are the first stage of human testing. The primary goal is to assess safety and determine appropriate dosage levels. Participants are closely monitored. These trials typically involve a small number of volunteers.
Is NCT06233110 currently recruiting?
Yes, NCT06233110 is actively recruiting participants. Contact the research team at chenyu.lin@duke.edu for enrollment information.
Where is the NCT06233110 trial being conducted?
This trial is being conducted at Durham, United States.
Who is sponsoring the NCT06233110 clinical trial?
NCT06233110 is sponsored by Stefanie Sarantopoulos, MD, PhD.. The principal investigator is Chenyu Lin, MD at Duke Health. The trial plans to enroll 30 participants.